Synthesis methods known as split-and-mix, or split-and-recombine, are known and have been used for the synthesis of different molecules. Split-and-mix methods for synthesising polypeptides and other biochemical polymers have been disclosed e.g. in U.S. Pat. No. 5,723,598 directed to the generation of a library of bifunctional complexes comprising a polypeptide and an identifier oligonucleotide comprising tags in the form of a sequence of nucleotides identifying the amino acids which participated in the formation of the polypeptide. The methods are directed to chemical linkage of tags and do not disclose enzymatic linkage, such as ligation, of the nucleotide tags making up the identifier oligonucleotide.
WO 00/23458 discloses a split-and-mix method in which nucleic acid tags are involved in both molecule synthesis and molecule identification.
WO 2004/039825 and WO 2005/058479 disclose split-and-mix methods wherein tags in the form of identifier oligonucleotides are linked enzymatically. The prior art methods do not disclose ligation of a double-stranded oligonucleotide substrate comprising a plurality of tags and complementary anti-tags at least partly hybridised to each other, wherein said ligation results in the formation of an identifier oligonucleotide comprising a plurality of consecutive nucleotides in the form of covalently linked tags, whereas the anti-tags of the double-stranded oligonucleotide substrate are not affected by the action of the ligase, i.e. no anti-tags become covalently linked as a result of the enzymatic ligation of the tag part of the double-stranded oligonucleotide substrate.
Reference is also made to WO2006/053571 disclosing methods for molecule synthesis.